期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 316, 期 2, 页码 601-607出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.105.093583
关键词
-
资金
- FIC NIH HHS [TW7180] Funding Source: Medline
- NINDS NIH HHS [NS40698] Funding Source: Medline
Nerve injury results in neuropathic pain, a debilitating pain condition. Whereas cannabinoids are consistently shown to attenuate neuropathic pain, the efficacy of opioids is highly controversial. Molecular mechanisms underlying analgesic effects of opioids and cannabinoids are not fully understood. We have shown that the signaling molecule ERK (extracellular signal-regulated kinase) is activated by C- fiber stimulation in dorsal horn neurons and contributes to pain sensitization. In this study, we examined whether opioids and cannabinoids can affect C-fiber-induced ERK phosphorylation (pERK) in dorsal horn neurons in spinal cord slices from normal and spinal nerve-ligated rats. In normal control spinal slices, capsaicin induced a drastic pERK expression in superficial dorsal horn neurons, which was suppressed by morphine (10 mu M), the selective mu-opioid receptor agonist DAMGO [[D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (1 mu M)], and the selective CB1 receptor ACEA agonist [arachidonyl-2'-chloroethylamide (5 mu M)]. One week after spinal nerve ligation when neuropathic pain is fully developed, capsaicin induced less pERK expression in the injured L-5-spinal segment. This pERK induction was not suppressed by morphine (10 mu M) and DAMGO (1 mu M) but was enhanced by high concentration of DAMGO (5 mu M). In contrast, ACEA (10 mu M) was still very effective in inhibiting capsaicin-induced pERK expression. In the adjacent L-4 spinal segment, both DAMGO and ACEA significantly suppressed pERK induction by capsaicin. These results indicate that, after nerve injury, opioids lose their capability to suppress C-fiber-induced spinal neuron activation in the injured L-5 but not in the intact L-4 spinal segment, whereas cannabinoids still maintain their efficacy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据